REACTIVE INTERMEDIATES IN PHOTOCHEMICAL REACTION OF BIOLOGICALLY RELEVANT PURINES

生物相关嘌呤光化学反应中的反应中间体

• 批准号: 6219053
• 负责人: RAFAEL ARCE
• 金额: $ 0.94万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219053
• 关键词: DNA damage; chemical models; dinucleotide; electron spin resonance spectroscopy; flash photolysis; high performance liquid chromatography; lasers; nuclear magnetic resonance spectroscopy; photoactivation; photochemistry; polynucleotides; purine nucleosides; purine nucleotides; purines; radiobiology; ultraviolet radiation

According to the American Cancer Society, more than 600,000 new cases of skin malignancies will be diagnosed in the U.S. each year. These as well as aging and disorders in the immune system are examples of photooxidatiave modifications to genomic DNA as a result of exposure of living organisms to solar UV radiation. At the molecular level these deleterious effects have been explained in terms of photoinduced base lesions in the nucleic acids. There have been reports of purine photoproducts in UV irradiated DNA which could also lead to these deleterious effects. Stable products of the purine moieties of DNA or reactive intermediates participating in the photochemical processes have not been studied in the same detail as is the case of the pyrimidine bases. In this continuation proposal our main objectives are to: 1. Isolate and characterize the products in the photodestruction mechanism of purine derivatives. These will be correlated to their short lived intermediates already identified and compared to products formed during high intensity nanosecond laser irradiation. 2. Identify intermediates and characterize products in the purine photoinitiated cross-linking reactions with molecules considered to be models for the side chain of amino acids and with amino acids. 3. Study reactions of reactive free radicals produced by the UV photoionization of purines such as the radical cation and the radical anion with biomolecules and to establish their extent of participation in the photodegradation mechanism. All this information will help to understand the role of purines in the DNA photochemistry.

根据美国癌症协会的数据，超过60万新病例 在美国，每年都会被诊断出皮肤恶性肿瘤。这些 以及免疫系统的老化和紊乱都是 暴露对基因组DNA的光氧化修饰 生物体对太阳紫外线辐射的影响。在分子水平上 这些有害的影响可以从光诱导的角度来解释 核酸中的碱基损伤。有报道称有嘌呤 紫外线照射的DNA中的光产物也可能导致这些 有害的影响。DNA或DNA的嘌呤部分的稳定产物 参与光化学过程的活性中间体 没有像以前那样详细地研究 嘧啶碱基。在这份续订提案中，我们的主要目标 目标是： 1.光解产物的分离和表征 嘌呤类化合物的作用机理。这些将与他们的 已确定的短命中间体并与产品进行比较 在高强度纳秒激光照射下形成。 2.确定嘌呤中的中间体和产物的特征 光引发的与被认为是 氨基酸侧链和氨基酸的模型。 3.研究紫外线产生的反应性自由基的反应 自由基阳离子和自由基等嘌呤的光致电离 阴离子与生物分子的结合并确定它们的参与程度 在光降解机制中。所有这些信息都将有助于 了解嘌呤在DNA光化学中的作用。